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Verfasst von:Balint, Bettina [VerfasserIn]   i
 Guerreiro, R. [VerfasserIn]   i
 Carmona, S. [VerfasserIn]   i
 Dehghani, N. [VerfasserIn]   i
 Latorre, Anna [VerfasserIn]   i
 Cordivari, C. [VerfasserIn]   i
 Bhatia, K. P. [VerfasserIn]   i
 Bras, J. [VerfasserIn]   i
Titel:KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia
Verf.angabe:B. Balint, R. Guerreiro, S. Carmona, N. Dehghani, A. Latorre, C. Cordivari, K.P. Bhatia and J. Bras
Jahr:2020
Umfang:7 S.
Fussnoten:First published: 25 March 2020 ; Gesehen am 07.01.2022
Titel Quelle:Enthalten in: European journal of neurology
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 1994
Jahr Quelle:2020
Band/Heft Quelle:27(2020), 8, Seite 1471-1477
ISSN Quelle:1468-1331
Abstract:Background and purpose Despite recent advances in neurogenetics that have facilitated the identification of a number of dystonia genes, many familial dystonia syndromes remain without known cause. The aim of the study was to identify the cause of autosomal dominant tremulous myoclonus-dystonia in a UK kindred with affected individuals in three generations. Methods Known genetic causes of myoclonus-dystonia were excluded. We combined clinical and electrophysiological phenotyping with whole-exome sequencing and Sanger sequencing to identify candidate causal variants in a family with tremulous myoclonus-dystonia. Results The core phenotype consisted of childhood-onset dystonia predominantly affecting hands and neck, with a fast tremor with superimposed myoclonus and, in some individuals, subtle cerebellar signs. We identified a novel missense variant in potassium calcium-activated channel subfamily N member 2 (KCNN2) [NM_021614:c.1112G>A:p.(Gly371Glu)], which was the only variant that we were able to identify as segregating with the phenotype over three generations. This variant, which is absent from the most recent version of gnomAD, was predicted to be deleterious by SIFT and PolyPhen-2 and had an overall CADD score of 29.7. Conclusions KCNN2, a member of the KCNN family of potassium channel genes, is highly conserved across species and in humans is highly expressed in the brain, particularly the cerebellum. KCNN2 mutations have never been described as pathological in human disease, but are recognized abnormalities in two rodent models of fast, jerky tremor. Segregation, absence of the variant in the normal population and in-silico prediction of a deleterious effect together with animal models compatible with the clinical phenotype are all in line with KCNN2 mutations being a plausible cause underlying myoclonus-dystonia.
DOI:doi:10.1111/ene.14228
URL:kostenfrei: Volltext ; Verlag: https://doi.org/10.1111/ene.14228
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.14228
 DOI: https://doi.org/10.1111/ene.14228
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:dystonia
 frissonnant
 KCNN2
 Kyoto rats
 myoclonus
 tremor
K10plus-PPN:1785231383
Verknüpfungen:→ Zeitschrift
 
 
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